| The Effect of Tissue Plasminogen Activator on TGF-beta1 Pre-Treated Human Mesothelial Cell Line. |
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Junglim Lee, Soo Jin Jeon, Young Choon Yoo, Ji Hye Kim, Yu Mi Lee, Sun Jung Kwon, Ji Woong Son, Eugene Choi, Moon Jun Na |
1Department of Microbiology, Konyang University College of Medicine, Daejeon, Korea.
2Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea. mjnamd@hanmail.net
3Myunggok Research Institute of Medical Science, Konyang University College of Medicine, Daejeon, Korea. |
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| Abstract |
BACKGROUND
In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-beta1 in a human pleural mesothelial cell line, MeT-5A. METHODS: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-beta1 for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. RESULTS: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-beta1 increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. CONCLUSION: TGF-beta1 is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-beta1 stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production. |
| Key Words:
Humans, Mesothelium, Cell Line, Tissue Plasminogen Activator, Transforming Growth Factor, Collagen |
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